Fluid dispensing device

ABSTRACT

The invention concerns a fluid dispensing device, characterised in that it comprises: a dispensing member ( 10 ) including: a conduit ( 42, 44 ) allowing through a transporting liquid ( 52 ), a valve ( 48 ) fixed to one of the ends ( 38 ) of said conduit, a dispensing needle ( 12 ) arranged at the other end ( 38 ), means for measuring the flow rate ( 46 ) of the transporting liquid ( 52 ) in the conduit, control means ( 54 ) for circulating the said liquid through said conduit in one direction or the other, and electronic means ( 58, 60 ) reacting to said measuring means ( 46 ) and acting both on said valve ( 48 ) and said control means ( 54 ) to cause a specific amount of fluid ( 30 ) to be sucked into the needle ( 12 ), and then to be restored.

[0001] The present invention relates to fluid dispensing devices. Itrelates more especially to a device intended to deliver very smallvolumes, typically from 0.001 to a few μl, with great precision.

[0002] Such a device is described in U.S. Pat. No. 5,916,524. Itcomprises a needle for dispensing a fluid into a target and which isconnected to an assembly comprising:

[0003] a syringe forming a housing and equipped with a plunger actuatedby a stepping motor,

[0004] a tube connecting the syringe to the needle, and

[0005] a set of valves associated with the tube and, initially, allowingthe syringe to be filled from a container and then, commanding the flowof the fluid through the tube towards the needle, the amount dispensedbeing defined by the number of steps effected by the stepping motor.

[0006] In most applications, the fluid to be dispensed needs to be verypure. It is therefore expensive and tricky to handle. In addition, thequantities needed may be extremely small. Now, with the device describedhereinabove, the liquid passes from the container into the syringe, thenfrom the latter into the needle, through the tube and the valves. Thevolume thus involved and the risk of contamination are great.Furthermore, it is difficult to control the amount dispensed. This isbecause the volume of fluid lying between the syringe and the end of theneedle is great and can vary appreciably, particularly throughdeformation of the tube when this tube is flexible.

[0007] Another device, which is similar, is described in U.S. Pat. No.5,927,547. It comprises:

[0008] a dispenser formed of a piezoelectric micro-dosing device,

[0009] a syringe fitted with a plunger and forming a housing, controlledby a stepping motor,

[0010] a pressure sensor, and

[0011] first and second tubes respectively connecting the syringe to thesensor and connecting the sensor to the micro-dosing device.

[0012] In this device, the syringe, the sensor and the first tube,together with part of the second tube, contain a transporter liquid. Afluid for dispensing, in this case a liquid also, arranged in a source,is drawn up by the plunger into the micro-dosing device as far as thesecond tube, with an air bubble interposed between the transporterliquid and the fluid.

[0013] The fluid for dispensing is ejected from the micro-dosing deviceby applying a signal to the piezoelectric part, which generates ashockwave causing a droplet of known volume, dependent on the dimensionsof the micro-dosing device and on the characteristics of the fluidconcerned, to be emitted.

[0014] Control means check, via the sensor, that the pressure of thetransport liquid remains constant, thus ensuring correct operation ofthe micro-dosing device. This pressure is adjusted by sending pulses tothe stepping motor, which controls the plunger of the syringe. In orderto dispense fluid only into charged targets, the micro-dosing device hasa capacitive level sensor at its free end.

[0015] The piezoelectric micro-dosing device allows very small volumes,which may be of the order of 5 picolitres, to be delivered. The maximumachievable flow rate is unfortunately limited, which means that the timetaken to dispense quantities of fluid of the order of a μl makes such adevice somewhat lacking. In addition, the volume available in themicro-dosing device is relatively modest, which means that if excessivenumbers of movements between the source and the target are to beavoided, the fluid for dispensing needs to be loaded not only into themicro-dosing device, but also into the tube connecting it to the sensor.There is therefore also a certain risk of contamination.

[0016] It should finally be pointed out that the use of a piezoelectricsystem for commanding the ejection of the fluid for dispensing gives thedevice a discrete operation which necessarily limits its precision.

[0017] Document WO 98/45205 proposes an improved version of the deviceaccording to U.S. Pat. No. 5,927,547. In this case, the transporterliquid is displaced by placing its reservoir at a reduced pressure, sothat a determined quantity of fluid is drawn up into the piezoelectricmicro-dosing device under the control of a flow sensor.

[0018] Such a device does, however, still suffer from the use of apiezoelectric dosing device for ejecting the fluid that is to bedispensed.

[0019] The object of the present invention is to propose a dispensingdevice that does not use a piezo micro-dosing device or equivalentelement. This object is achieved by virtue of the fact that itcomprises:

[0020] a duct for the passage of a transporter liquid,

[0021] a valve fixed to one of its ends,

[0022] a dispensing needle arranged at its other end,

[0023] means of measuring the rate of flow of the transporter liquid inthe duct,

[0024] a sealed container containing the transporter liquid andconnected to the valve by a tube,

[0025] a pump of the intake and delivery type, in communication with thecontainer and serving to place the latter at a raised pressure or at areduced pressure so as to cause the liquid to flow through the said ductin one direction or the other, and

[0026] electronic means responding to the said flow measurement meansand acting both on the said valve and on the said pump so as to cause adetermined amount of fluid to be drawn up into the needle thendelivered.

[0027] In such a dispensing device, the fluid is drawn up and ejectedonly under the command of the measuring means of the rate of flow of thetransporter liquid, by placing the container of said liquid at a reducedpressure or at a raised pressure. Thus, it is no longer necessary, as itis the case with devices according to documents U.S. Pat. No. 5,927,547and WO 98/45205, to associate the needle with a piezoelectric system andthe high voltage electronic circuit which controls it.

[0028] The cost of the device is thus strongly reduced and itsreliability is improved. Moreover, the ejection of the fluid by a merely“passive” needle insures a continuous mode of operation whereas theejection by a piezo is made in a discrete way. The precision is thusimproved. Advantageously, the duct is formed inside an elongate bodybearing, at its respective ends, the valve and the needle and, in itscentral portion, the said flow measurement means which are inserted inthe path of the duct, in communication therewith. The dispensed volumeis thus measured in the optimum way.

[0029] For certain applications, in which very small volumes are used,experience has shown that it is advantageous for the duct to be formedinside an elongate body bearing, at its respective ends, the valve andthe needle and for the flow measurement means to be inserted in the pathof the duct, upstream of the valve.

[0030] According to a preferred embodiment, the flow measurement meansare of the type that provides a measurement of the pressure differencebetween two points on the duct and a measurement of the temperature.

[0031] In this embodiment, the electronic means may be designed toanalyse information from the flow measurement means and to provideinformation on the conditions of dispensing of the fluid.

[0032] The electronic means advantageously comprise:

[0033] means of calculating the amount of fluid drawn into or deliveredthrough the needle, on the basis of the information supplied by the flowmeasurement means, and

[0034] a control circuit placed under the command of the saidcalculating means and mainly performing the functions of controlling thepump to place the said container at a raised pressure or at a reducedpressure and of commanding the opening and closing of the valve so as toallow or disallow the displacement of a determined amount of transportliquid in one direction or the other.

[0035] As a preference, the calculating means hold, in memory, thevalues of the viscosity of the transport liquid as a function oftemperature and are programmed to calculate, on the basis of thepressure and temperature information delivered by the said flowmeasurement means, the amount of fluid drawn into or delivered throughthe needle.

[0036] Finally, it is particularly advantageous for the electronic meansto be designed, in addition, to detect that a drop of fluid attached tothe end of the needle is in contact with a target.

[0037] It is useful to note that the device as described hereinabovemakes it possible precisely to measure the volume of fluid both when itis drawn up and when it is dispensed. It is thus possible to preparedoses of one or several fluids, separated by an air bubble, these dosesthen being dispensed into the targets.

[0038] Other advantages and features of the invention will becomeapparent from the description which will follow, given with respect tothe appended drawing, in which:

[0039]FIG. 1 is the operating diagram of a fluid dispensing device inits surroundings, and

[0040]FIG. 2 shows, in greater detail, the structure of the deviceaccording to the invention.

[0041]FIG. 1 shows, schematically, an assembly comprising a fluiddispenser 10 equipped with a dispensing needle 12 and a control cabinet14. A tube 16 and a cable 18 connect the dispenser 10 to the cabinet 14.

[0042] The assembly further comprises a robot 20 of the Cartesian type,formed of a horizontal table 22, of a portal frame 24 mounted so that itcan move in translation over the table in a direction perpendicular tothe plane of the figure, and of a carriage 26 mounted so that it canmove in horizontal translation along the portal frame in a directionparallel to the plane of the figure. The dispenser 10 is mounted so thatit can move in vertical translation on the carriage 26, so that it canthus move along three mutually orthogonal axes. A source 28 containing afluid 30 and a target 32 are arranged on the table 22, in the spaceswept by the portal frame 24.

[0043] The assembly depicted in FIG. 1 is intended to allow precisetransfer of the fluid 30, by means of the dispenser 10, from the source28 to the target 32.

[0044] Both the source 28 and the target 32 may be a test specimen, amicrotitration plate (of type 96, 384 or 1536 for example) or any othersurface or reservoir of liquid arranged in any spatial formatwhatsoever. The fluid 30 is generally a liquid, but could just as easilybe a gas. In this case, the source 28 is a sealed container closed by amembrane able to be perforated and the needle 12 is of a type similar tothose used for hypodermic injections, for example.

[0045] Reference will now be made to FIG. 2 which, in greater detail,shows the dispenser 10 and the control cabinet 14.

[0046] The dispenser 10 comprises a support 34 intended to be fitted tothe carriage 26 and bearing an elongate body 36, advantageously made ofchemically inert plastic, such as the material known by the name ofPEEK, of cylindrical overall shape and mounted vertically. At each endit has a cylindrical housing 38 and, in its central portion, it has acavity 40. It is also pierced, along its axis, with an upper duct 42opening, on the one hand, into the upper housing 38 and, on the otherhand, into the cavity 40 and with a lower duct 44 opening, on the onehand, into the lower housing 38 and, on the other hand, into the cavity40.

[0047] The cavity 40 houses a flow meter 46, made on a ceramic tabletand which is positioned in such a way as to find itself in sealedcommunication with the ends of the ducts 42 and 44. It is advantageouslyfixed by clamping, with the insertion of seals.

[0048] The upper housing 38 houses, in a sealed and removable manner,via an appropriate adapter, a valve 48 the function of which is to placethe upper duct 42 in communication with the tube 16.

[0049] At the other end of the body 36, the lower housing 38 houses,also in a sealed and removable manner, via an appropriate adapter, theend of the dispensing needle 12.

[0050] The needle 12 is chosen according to the way in which the fluid30 is to be dispensed to the target 32 and according to the volume to bedispensed, as will be specified later on.

[0051] The material of which the needle 12 is made must not react withthe fluid. Stainless steel may, for example, be used in many cases. Thebasic material may or may not be covered with a layer improving thewettability or non-wettability properties of certain internal orexternal surfaces of the needle.

[0052] The length and the bore of the needle 12 are chosen according tothe quantity of fluid to be dispensed to the target 32 in one or moreshots. These dimensions are defined in such a way that the volume of thebore of the needle is greater than the volume of fluid to be dispensedin a single shot. It is thus possible for the volume in question to bedrawn up in such a way that it is entirely housed in the needle,something which affords various advantages.

[0053] Specifically, once the fluid 30 can remain confined to the needle12, when there is a wish to dispense another fluid, all that is requiredis for this needle to be changed rather than for the whole dispenser tohave to be cleaned. It is thus possible, during one and the samesequence, to dispense several fluids, in highly varying quantities,without that posing any problem. To do this, all that is required is forthe needle to be changed, something that a robot can do with nodifficulty.

[0054] It is also possible to dispense highly corrosive fluids, simplyby choosing an appropriate needle.

[0055] In other words, these advantages stem from the fact that there isno interference between the fluid or fluids for dispensing and thecomponents of the dispenser 10 other than the needle 12.

[0056] The flow meter 46 plays an important part in the correctoperation of the device because it needs to be able, precisely, tomeasure a volume of a few nanolitres. It is advantageous for thispurpose to use the flow meter described in the publication entitled “ADifferential Pressure Liquid Flow Sensor for Flow Regulation and DosingSystems” by M. A. Boillat et al. 0-7803-2503-6© 1995 IEEE. This flowmeter comprises sensors making it possible to measure a pressuredifference between its inlet and its outlet, and the temperature of thefluid passing through it. Once these two parameters have beendetermined, it is possible to calculate the flow rate, provided that theviscosity of the transport liquid as a function of its temperature isknown.

[0057] As FIG. 2 shows, the control cabinet 14 comprises a sealedcontainer 50 partially filled with a transport liquid 52 into which thetube 16 connected to the valve 48 dips. A pump 54, of the intake anddelivery type, is in communication, via a duct 56, with the upper partof the container situated above the liquid 52.

[0058] The liquid 52 is chosen according to the fluid 30 for dispensingso that these liquids are, from the chemical point of view, neutral withrespect to each other. It will be noted that the liquid 52 fills thetube 16 and passes through the dispenser 10 as far as the needle 12, aswill be specified later on.

[0059] The pump 54 allows the container 50 to be placed at a raisedpressure or at a reduced pressure. In that way, when the valve 48 isopened, the liquid 52 can be displaced from the container 50 to theneedle 12 or in the other direction.

[0060] A control circuit 58 is connected to the pump 54, to the valve 48and to the flow meter 46. It is under the command of a computer 60 toperform the following main functions:

[0061] controlling the pump 54 with a view to placing the container 50at a raised pressure or at a reduced pressure,

[0062] commanding the opening and closing of the valve 48 allowing ordisallowing the displacement of the liquid 52 in one direction or theother,

[0063] transmitting to the computer 60 the pressure and temperaturemeasurements from the flow meter 46.

[0064] The computer 60 serves to program and coordinate the assembly. Itthus controls the movements of the robot 20 to cause the dispenser 10 togo and find doses of fluid 30 from the source 28 and deposit them on thetarget 32. In addition, it holds in its memory the values of theviscosity of the transport liquid as a function of temperature. Thatallows it, on the basis of the pressure and temperature informationdelivered by the flow meter 46, to determine, precisely and in realtime, the amount of fluid drawn up into or delivered through the needle12. It is thus possible to retain in memory the exact quantities offluid 30 dispensed each time. Furthermore, analysis of the signalsemitted by the flow meter 46 makes it possible to detect malfunctions inthe device, such as sealing problems or problems of blockages in theducts 42 or 44.

[0065] The device which has just been described allows a fluid 30 to betransferred between the source 28 and the target 32 in a particularlyeffective and economical way. This operation is performed as follows.

[0066] First of all, the transporter liquid 52 is introduced into thecontainer 50. The latter is then closed and the pump 54 is activated, soas to place the container 46 at a raised pressure. The valve 48 is thenopened, so that the liquid 52 enters the tube 16 and passes through thedispenser 10 as far as the needle 12 which it completely fills. Thevalve 48 is then closed.

[0067] During this operation it is essential to make sure that no airbubbles remain trapped in the tube 16, as this would degrade theperformance of the device. This check can be done automatically, byanalysing the signals emitted by the flow meter. Indeed it is found thatthe presence of air bubbles leads to elasticity in the ducts 42 and 44,and this slows the pressure rise when the valve is open.

[0068] The device 10 is now ready to take fluid 30 from the source 28 todeliver it to the target 32. For this, the container 50 is placed at areduced pressure by the pump 54 and the robot 20 brings the needle 12over the source 28.

[0069] According to an advantageous mode of operation, a small amount ofair is first of all drawn up by the needle 12 so as to form a bubblebetween the liquid 52 and the fluid 30 for dispensing. For this, thevalve 48 is opened and the liquid 52 rises up in the needle 12 towardsthe container 50, through the flow meter 46 whose output signal allowsthe control circuit 58 to calculate the volume of air drawn in, that isto say the volume of the bubble. When the measured volume reaches thedesired value contained in the computer 60, the valve 48 is closed andthe robot 20 introduces the needle 12 into the fluid 30.

[0070] When the latter is a liquid, which it generally is, the flowmeter 46 records a sudden variation in pressure when the needle 12 goesin. The computer 60 can thus determine the position of the needle 12with respect to the surface of the fluid 30. It then gives the robot 20the order to plunge the needle 12 into the fluid 30 far enough to avoidthe formation of parasitic bubbles during suction. The valve is thenopened again so that the drawing-up operation can begin.

[0071] When, on the basis of the information supplied by the flow meter46, the computer 60 determines that the desired amount of fluid has beendrawn up into the needle 12, the valve 48 is closed again.

[0072] It is possible to repeat this operation several times so that theneedle 12 can contain several doses of fluid 30, each separated by anair bubble.

[0073] As an alternative, the fluid 30 can be drawn up without theinterposition of an air bubble. The needle 12 is then plunged directlyinto the fluid 26 and the drawn-up volume is determined as describedabove, but in a single shot.

[0074] When the needle 12 is filled with the fluid for dispensing, therobot 20 takes the dispenser 10 over the target 32 and the pump 54places the container 50 at a raised pressure. The valve 48 is thenopened to allow the fluid to be ejected and closed again when themeasured volume corresponds to the volume set by the computer.

[0075] The dimensions of the needle bore play an important part,especially when the end of this needle is in the air. In this case,precise dispensing can be achieved only if the fluid 30 flows outuniformly. What this amounts to is that it is necessary to avoid dropsforming during the dispensing operation. A suitable choice of thepressure in the container 50 and of the bore at the free end of theneedle 12 allows satisfactory operation to be ensured.

[0076] When a small volume needs to be dispensed, it is advantageous touse a needle having a narrowing of the hole at its free end, this beingwell known by the term “nozzle”. It is also advantageous for the flowmeter 46 to be upstream of the valve 48. Indeed, experience has shownthat the flow can be well controlled in this way, even with low flowrates.

[0077] It goes without saying that the device according to the inventioncan be used in yet other conditions. It is thus also possible todispense a gas. In this case, the needle is introduced into a sealedbottle, in place of the source 24, which contains the gas and theliquid. A volume of gas is drawn up, as explained above with regard tothe air, followed by a drop of liquid, so that the gas is trapped in theneedle by successive bubbles of tailored volume. This gas is thendispensed into a target by injecting into it a volume corresponding tothe volume of the gas and of the drop separating two successive bubbles.

1. Fluid dispensing device characterized in that it comprises: adispensing member (10) comprising: a duct (42, 44) for the passage of atransporter liquid (52), a valve (48) fixed to one of the ends (38) ofthe said duct, a dispensing needle (12) arranged at the other end (38),and means (46) of measuring the rate of flow of the transporter liquid(52) in the duct, a sealed container (50) containing the transporterliquid (52) and connected to the valve (48) by a tube, a pump (54) ofthe intake and delivery type, in communication with the container (50)and serving to place the latter at a raised pressure or at a reducedpressure so as to cause the transporter liquid (52) to flow through thesaid duct (42, 44) in one direction or the other, and electronic means(58, 60) responding to the said measurement means (46) and acting bothon the said valve (48) and on the said pump (54) so as to cause adetermined amount of fluid (30) to be drawn up into the needle (12) thendelivered.
 2. Fluid dispensing device according to claim 1,characterized in that the said duct (42, 44) is formed inside anelongate body (36) bearing, at its respective ends (38), the said valve(48) and the said needle (12) and, in its central portion (40), the saidflow measurement means (46) which are inserted in the path of the duct(42, 44), in communication therewith.
 3. Fluid dispensing deviceaccording to claim 1, characterized in that the said duct (42, 44) isformed inside an elongate body (36) bearing, at its respective ends(38), the said valve (48) and the said needle (12), and in that the saidflow measurement means are inserted in the path of the duct (42)upstream of the said valve (48), in communication with this duct. 4.Fluid dispensing device according to claim 1, characterized in that thesaid flow measurement means (46) are of the type that provides ameasurement of the pressure difference between two points on the ductand a measurement of the temperature.
 5. Fluid dispensing deviceaccording to claim 4, characterized in that the said electronic means(58, 60) are designed to analyse information from the flow measurementmeans (46) and to provide information on the conditions of dispensing ofthe said fluid.
 6. Fluid dispensing device according to one of claims 1to 5, characterized in that the said electronic means (58, 60) comprise:means (60) of calculating the amount of fluid drawn into or deliveredthrough the needle, on the basis of the information supplied by the flowmeasurement means, and a control circuit (58) placed under the commandof the said calculating means (60) and mainly performing the functionsof controlling the pump (54) to place the said container (50) at araised pressure or at a reduced pressure and of commanding the openingand closing of the valve (48) so as to allow or disallow thedisplacement of a determined amount of transport liquid (52) in onedirection or the other.
 7. Fluid dispensing device according to claims 4and 6, characterized in that the said calculating means (60) hold, inmemory, the values of the viscosity of the transport liquid (52) as afunction of temperature and are programmed to calculate, on the basis ofthe pressure and temperature information delivered by the said flowmeasurement means (46), the amount of fluid drawn into or deliveredthrough the needle (12).
 8. Fluid dispensing device according to claim5, characterized in that the said electronic means (58, 60) aredesigned, in addition, to detect that a drop of fluid attached to theend of the needle (12) is in contact with a target (32).